Previously Unappreciated Function of αE-catenin Uncovered by Cirulli and Crisa Labs

Work in the Cirulli and Crisa Labs has uncovered a previously unappreciated function of αE-catenin, a key component of cell-cell junctions, in the development of pancreatic endocrine cells. The study, featured in the journal cover of Cell Reports, reports that in the absence of αE-catenin multipotent pancreatic progenitors loose the ability to form stable cell-cell contacts, and undergo untamed proliferation. The investigators discovered that these defects are caused by a constitutive activation of the sonic hedgehog signaling pathway (SHH) which leads to the accumulation of Sox9+ pancreatic progenitors and failure to mature into insulin-producing beta-cells. Pharmacological blockade of the SHH pathway rescues these defects and restores the development of insulin-producing pancreatic beta-cells. These discoveries reveal a crucial function of αE-catenin in pancreatic islet development, and harbor significant implications for the design of beta-cell replacement and regeneration therapies in diabetes, and possibly for the identification of new therapeutic targets in pancreatic precancerous lesions.

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Jimenez-Caliani et al., 2017, Cell Reports20, 1295–1306August 8, 2017ª2017 The Authors.


This study was supported by JDRF grants #1-2005-1084 and #1-2004-13, by the WA State Life Sciences Discovery Fund Program grant #4553677, and by R01 DK103711-01; L.C. was supported by RO1 HL075270 and WA StateLife Sciences Discovery Fund Program grant #4553677;